Letter abstract
Nature Cell Biology 8, 1448 - 1454 (2006)
Published online: 19 November 2006 | doi:10.1038/ncb1513
Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells
Rabindranath De La Fuente1, Claudia Baumann1, Tao Fan3, Anja Schmidtmann3, Ina Dobrinski2 & Kathrin Muegge3
Lymphoid specific helicase (Lsh) is a major epigenetic regulator that is essential for DNA methylation and transcriptional silencing of parasitic elements in the mammalian genome1, 2. However, whether Lsh is involved in the regulation of chromatin-mediated processes during meiosis is not known. Here, we show that Lsh is essential for the completion of meiosis and transcriptional repression of repetitive elements in the female gonad. Oocytes from Lsh knockout mice exhibit demethylation of transposable elements and tandem repeats at pericentric heterochromatin, as well as incomplete chromosome synapsis associated with persistent RAD51 foci and 
H2AX phosphorylation. Failure to load crossover-associated foci results in the generation of non-exchange chromosomes. The severe oocyte loss observed and lack of ovarian follicle formation, together with the patterns of Lsh nuclear compartmentalization in the germ line, demonstrate that Lsh has a critical and previously unidentified role in epigenetic gene silencing and maintenance of genomic stability during female meiosis.
- Female Germ Cell Biology Group, Department of Clinical Studies, Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center, 382 West Street Road, Kennett Square, PA 19348, USA.
- Male Germ Cell Biology Group, Department of Clinical Studies, Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center, 382 West Street Road, Kennett Square, PA 19348, USA.
- Laboratory of Molecular Immunoregulation, SAIC-Basic Research Program, National Cancer Institute, Frederick, MD 21701, USA.
Correspondence to: Rabindranath De La Fuente1 e-mail: rfuente@vet.upenn.edu
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